David S. Celermajer

Objective: Left ventricular diastolic dysfunction (LVDD) is commonly associated with pulmonary hypertension (PHT); however, the factors associated with the presence and severity of PHT in patients with LVDD have not been well characterised. Methods: We analysed the profiles and echo characteristics of 16 058 adults with LVDD and preserved left ventricular ejection fraction (LVEF, >50%) from the National Echocardiography Database of Australia. Peak tricuspid regurgitation velocity (TRV) was used to determine the presence of PHT. Univariate and multivariate analyses were performed to evaluate the parameters associated with the presence/increasing severity of PHT. Results: Mean age was 73±12 years and 9216 (57.4%) were women. 2503 (15.6%) subjects had atrial fibrillation (AF) and 13 555 (84.4%) were in sinus rhythm. Overall, 9976 (62.1%) had PHT (TRV >2.9 m/s). There was a progressive increase in indexed left atrial volume with rising TRV levels. AF and right ventricular (RV) dilation were strongly associated with the presence of PHT (adjusted OR (aOR) 1.27 (95% CI 1.12 to 1.43) and aOR 4.99 (95% CI 4.44 to 5.62), respectively). Increased age, LVEF and body mass index were also independently associated with PHT (p<0.001). On multivariate analysis, older age, female sex, AF, lower E/e' and LVEF were independently associated with the severity of PHT (p<0.001). The presence of AF increased the TRV by an average of 0.32 m/s, RV dilation by 1.82 m/s, female sex by 0.32 m/s and age (per decade) by 0.3 m/s. Conclusions: In this large study, PHT was common in LVDD and was strongly associated with the presence of enlarged left atrium, AF and older age, in particular.

Objective: Lipoprotein(a) [Lp(a)] has regained attention as an independent cardiovascular risk factor, particularly given emerging therapies entering late-phase clinical trials. Here, we aim to examine the association of Lp(a) with CAD and the potential of Lp(a) as an enrichment criterion for identifying individuals more likely to benefit from screening for subclinical CAD with CT imaging. Methods: We analysed data from 1,718 adults undergoing CTCA for suspected CAD enrolled in the BioHEART study. Lp(a) levels were measured, and CAD burden was assessed using coronary artery calcium score (CACS) and Gensini scores. Plaque morphology for the most stenotic plaque of each Gensini segment was classified as calcified, non-calcified or mixed. Youden's index with 10,000 bootstraps was used to identify the optimal threshold for increased risk of clinically actionable CAD. Results: Lp(a) was strongly associated with all CTCA measures of CAD examined. Elevated Lp(a) above 22 nmol/L was linked to more advanced multi-segment (ordinal OR = 1.14 [1.03-1.25]) and multivessel disease (ordinal OR = 1.11 [1.02-1.20]), with a 2.6% increased risk of a CACS >100 for every 10 nmol/L increment. Lp(a) was most strongly associated with mixed plaque burden even after adjusting for traditional risk factors (β = 4.75, p=0.001), but not with non-calcified or calcified plaque. Adding Lp(a) to standard risk models resulted in an overall NRI of 16% [0.06-0.27] and 42% [0.16-0.70] in patients without standard modifiable risk factors. Conclusions: Our findings suggest Lp(a)'s role in a new clinical pathway: screening patients considered low or intermediate risk, particularly those without standard modifiable risk factors for non-invasive imaging to detect subclinicalCAD.

To compare the outcomes for repaired tetralogy of Fallot and Fontan patients who must travel from regional Victoria and interstate, in order to receive specialist congenital heart disease (CHD) surgery and ongoing care, with those of local patients. This retrospective study included 332 patients who underwent tetralogy of Fallot (ToF) repair and 159 patients who underwent a Fontan procedure at Royal Children's Hospital (RCH) Melbourne between 2003 and 2017. Data was obtained from the National CHD Registry, linked with National Death Index data, and follow-up data from the Australian and New Zealand Fontan Registry. Equivalent outcomes were observed between location groups in both cohorts for all of the main outcomes of interest. Repaired ToF subjects were aged 0.76 years (IQR 0.52-3.33) at operation and 10.2 years (IQR 5.46-14.9) at last follow-up, whilst Fontan subjects were aged 4.94 (IQR 4.27-5.66) years at operation and 14.2 years (IQR 11.3-16.4) at last follow-up. Mortality rates were extremely low and did not significantly differ between geographic groups, with 10-year survival in the repaired ToF cohort 98.0 % in the City group, 98.1 % in the Regional group, and 98.8 % in the Interstate group; and 97.8 %, 92.3 %, and 97.5 % in the Fontan cohort, respectively. In the Australian setting and with adequate planning and local follow-up options, patients travelling from regional areas or interstate for their CHD operations have similar outcomes, out to 21 years, compared to patients living locally.

Objective: To examine global and health-related quality of life (QOL) among parents of individuals with Fontan physiology and determine associations with sociodemographic, parent and child-related health, psychological, and relational factors. Methods: Parents participating in the Australian and New Zealand Fontan Registry (ANZFR) QOL Study (N = 151, Parent Mean age = 47.9 ± 10.2 years, age range: 31.6-79.6 years, 66% women; child Mean age = 16.3 ± 8.8, age range: 6.9-48.7 years, 40% female) completed a series of validated measures. Health-related QOL was assessed using the PedsQL 4.0 Core Generic Scales for adults and global QOL was assessed using a visual analogue scale (0-10). Results: Most parents (81%) reported good global QOL (≥ 6), consistent with broader population trends. Nearly one-third of parents (28%) reported at-risk health-related QOL (based on total PedsQL scores) with physical functioning most affected (44%). Psychological factors, including psychological stress and sense of coherence, emerged as the strongest correlates of global and health-related QOL, explaining an additional 16 to 30% of the variance (using marginal R2). Final models explained 35 and 57% and of the variance in global and health-related QOL, respectively (marginal R2). Relational factors, including perceived social support and family functioning contributed minimally when analyzed alongside psychological variables. Conclusions: While parents of individuals with Fontan physiology report good global QOL, challenges in health-related QOL exist. We identified key psychological, sociodemographic, and health-related factors associated with parental QOL outcomes. These data may aid early identification of physical and psychosocial difficulties and guide targeted health resource allocation for this population.

Rheumatic heart disease remains a major health problem for Aboriginal and Torres Strait Islander peoples. In this Reflection, potential solutions to this lamentable situation are reviewed.